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OxPCs‐Mediated Lipid Metabolic Responses in Cardiomyocytes as well as During Ischemia Reperfusion Injury
Author(s) -
Bagchi Ashim K,
Surendran Arun,
Ravandi Amir,
Jassal Davinder,
Singal Pawan K
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb480
Subject(s) - downregulation and upregulation , oxidative stress , chemistry , inflammation , proinflammatory cytokine , receptor , medicine , endocrinology , ex vivo , microbiology and biotechnology , homeostasis , ischemia , tlr2 , biology , biochemistry , tlr4 , in vitro , gene
Oxidized phospholipids (OxPLs) promote inflammation as well as low density lipoprotein (LDL) uptake through its receptor (LOX‐1) in a variety of physiological and pathological states. We investigated whether the proinflammatory effect of OxPL, generated during stress conditions such as ex‐vivo exposure to POVPC (1‐Palmitoyl‐2‐(5‐oxovaleroyl)‐sn‐glycero‐3‐phosphorylcholine), a derivative of oxidative phosphatidylcholines (OxPCs) of OxPL family and global heart ischemia/reperfusion (I/R), is through the activation of LOX‐1 as well as toll‐like receptor‐2 (TLR‐2). In this study, isolated cardiomyocytes exposed to POVPC as well as isolated rat hearts subjected to global I/R were analyzed. OxPCs‐mediated‐oxidative stress (OS), caused LOX‐1 activation and altered lipid homeostasis. There was an upregulation of TLR2 expression in these conditions, suggesting that TLR2‐mediated inflammation is through LOX1. Furthermore, phosphorylation of sterol regulatory element binding protein 1c (SREBP 1c) was also found be increased due to an increase in OxPCs levels, which is also promoted OS and cell death. On the other hand, LOX‐1 activation also upregulated SREBP1c‐mediated TGF‐βRII expression causing fibrosis. Out of 80 fragmented and non‐fragmented OxPCs followed in a heatmap analysis, 24 in cardiomyocytes and 25 in heart were significantly higher in these stress conditions. Eight (8) of the OxPCs were shared between cardiomyocytes and hearts (FDR < 0.001). Interestingly, one specific fragmented OxPC i.e. 1‐palmitoyl‐2‐azelaoyl‐sn‐glycero‐3‐phosphocholine (PAzPC) among 8 shared OxPCs, was common in both stress conditions. However, a second major fragmented OxPC i.e. 1‐stearoyl‐2‐azelaoyl‐sn‐glycerophosphocholine (SAzPC) was also upregulated in the heart but not in the cardiomyocyte. It appears that cardiomyocyte‐specific; PAzPC and heart‐specific; SAzPC OxPCs may mediate abnormal lipid metabolic responses causing inflammation, apoptosis and fibrosis. Support or Funding Information Canadian Institutes of Health Research and Research Manitoba This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .